Maternal High-Fat Diet Alters Fetal Autonomic Activity Independently of Leptin Receptor Genotype in High-Risk Mouse Models of Type 2 Diabetes Mellitus.

BACKGROUND

The Developmental Origin of Health and Disease (DOHaD) concept suggests fetal environmental factors influence disease vulnerability later in life. Type 2 diabetes mellitus (T2DM), a metabolic disease, is associated with autonomic dysfunction. Some T2DM pathophysiological manifestations may exhibit DOHaD features and these autonomic changes could originate during fetal development.

OBJECTIVES

This study investigated genetic and environmental T2DM risks on fetal autonomic activity, focusing on leptin receptor gene mutation, maternal high-fat diet, and their interactions.

METHODS

Pregnant leptin receptor gene mutant (Leprdb) heterozygous mice received standard unpurified diet (normal diet, 11% energy from fat) or high-fat diet (60% energy from fat) from gestational day 0.5, whereas C57BL/6J mice received control diet (10% energy from fat) or high-fat diet to verify maternal dietary effects without genetic factors. Fetal electrocardiograms were measured at gestational day 18.5 to assess autonomic activity. The impact of intrauterine conditions due to maternal Leprdb genotype was also evaluated. Statistical analysis was performed using analysis of variance with main effects for fetal genotype, maternal diet, or maternal genotype to distinguish genetic and environmental factors.

RESULTS

When dams were fed normal diet, no difference in fetal autonomic activity was observed based on fetal Leprdb genotype. Similarly, no difference was found when dams were fed high-fat diet. However, maternal high-fat diet significantly reduced fetal autonomic activity, regardless of fetal Leprdb genotype. This pattern was confirmed in C57BL/6J mice, where fetuses exposed to maternal high-fat diet showed decreased autonomic activity. Maternal Leprdb genotype did not significantly influence fetal autonomic activity.

CONCLUSIONS

These findings indicate maternal high-fat diet during pregnancy may reduce fetal autonomic activity, potentially increasing T2DM risk. Environmental factors appear to impact fetal autonomic activity more than genetic factors. Maternal diet during pregnancy could be crucial for offspring's metabolic health, emphasizing proper maternal nutrition's importance for preventing metabolic disorders.